A Study to Evaluate the Efficacy and Safety of Autogene Cevumeran With Nivolumab Versus Nivolumab Alone in Participants With High-Risk Muscle-Invasive Urothelial Carcinoma (MIUC)
- Conditions
- Muscle Invasive Urothelial Carcinoma
- Interventions
- Registration Number
- NCT06534983
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
The main purpose of the study is to evaluate the efficacy of adjuvant treatment with autogene cevumeran plus nivolumab compared with nivolumab in participants with high risk MIUC.
In this study participants will be enrolled in a safety run-in phase to receive autogene cevumeran + nivolumab. This phase will be conducted to monitor and ensure the safety of study participants. After all participants in the safety run-in have been enrolled to receive autogene cevumeran + nivolumab, further participants will be randomization in either autogene cevumeran + nivolumab or the saline + nivolumab arm.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 362
- Histologically confirmed muscle-invasive UC (also termed TCC) of the bladder or upper urinary tract
- TNM classification (UICC/AJCC 7th edition) at pathological examination of surgical resection specimen of (y)pT3-4 or (y)pN+ and M0
- Surgical resection of MIUC of the bladder or upper tract
- Participants who have not received prior neoadjuvant cisplatin chemotherapy (NAC) must be ineligible to receive adjuvant cisplatin therapy due to patient refusal, cisplatin ineligibility or investigator decision
- Tumor tissue must be provided for biomarker analysis
- Absence of residual disease and absence of metastasis, as confirmed by a negative baseline Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan of the pelvis, abdomen, and chest no more than 28 days prior to randomization.
- Full recovery from cystectomy or nephroureterectomy within 120 days following surgery
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Negative HIV test at screening
- No evidence of active hepatitis B, defined as having a negative hepatitis B surface antigen (HbsAg) test at screening
- Negative hepatitis C virus (HCV) antibody test at screening, or a positive HCV antibody test followed by a negative HCV RNA test at screening
- Partial cystectomy in the setting of bladder cancer primary tumor or partial nephroureterectomy in the setting of renal pelvis primary tumor
- Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment
- Any prior neoadjuvant immunotherapy
- Adjuvant chemotherapy or radiation therapy for UC following surgical resection
- Malignancies other than UC within 5 years prior to randomization
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Saline+Nivolumab Nivolumab Participants will receive saline solution along with 480 milligrams (mg) of nivolumab, IV, once every 4 weeks (Q4W) for 1 year. Saline+Nivolumab Saline Participants will receive saline solution along with 480 milligrams (mg) of nivolumab, IV, once every 4 weeks (Q4W) for 1 year. Autogene Cevumeran + Nivolumab Nivolumab Participants will receive autogene cevumeran along with nivolumab intravenously (IV) at a recommended dose at specified timepoints. Autogene Cevumeran + Nivolumab Autogene Cevumeran Participants will receive autogene cevumeran along with nivolumab intravenously (IV) at a recommended dose at specified timepoints.
- Primary Outcome Measures
Name Time Method Investigator Assessed Disease Free Survival (INV-DFS) Randomization until the first recurrence of disease or death from any cause, whichever occurs first (approximately 6 years ) Disease recurrence is defined as any of the following:
* Local (pelvic) recurrence of urothelial carcinoma (UC) (including soft tissue and regional lymph nodes)
* Urinary tract recurrence of UC (excluding low-grade non-muscle-invasive bladder cancer (NMIBC))
* Distant metastasis of UC
- Secondary Outcome Measures
Name Time Method Investigator Assesed DFS in Programmed Death Ligand-1 (PD-L1) Expression ≥ 1% Population Randomization until first occurrence of a documented disease recurrence or death from any cause, whichever occurs first (approximately 6 years) Number of Participants With Symptomatic Treatment Toxicities as Assessed by National Cancer Institute Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE) From Day 1 up to Cycle 21 (cycle length=28 days) The PRO-CTCAE contains 124 questions that are rated either dichotomously (for determination of presence vs. absence) or on a 5-point Likert scale (for determination of frequency of occurrence, severity, and interference with daily function). Treatment toxicities can occur with observable signs (e.g., vomiting) or non-observable symptoms (e.g., nausea). A subset of 16 symptoms (fatigue, chills, nausea, vomiting, diarrhea, constipation, decreased appetite, swelling, itching, rash, headache, muscle pain, joint pain, general pain, cough, and shortness of breath) will be assessed.
Overall Survival (OS) Randomization until the date of death from any cause (approximately 6 years) Investigator Assessed Distant Metastasis-Free Survival (DMFS) Randomization to the date of diagnosis of distant (i.e., non-locoregional) metastases (approximately 6 years) Number of Participants with Adverse Events (AEs) Up to approximately 22 months Change From Baseline in Participant-reported Pain, Physical Function, Role Function and Quality of Life (QoL) as Assessed Using European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30) From Day 1 up to approximately 25 months The EORTC QLQ-C30 consists of 30 questions that assess five aspects of participant functioning scale, three symptom scales, global health status (GHS), QoL, and single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Scale scores can be obtained for the multi-item scales. The functioning and symptoms items are scored on a 4-point scale that ranges from "not at all" to "very much", and the GHS and QoL items are scored on a 7-point scale that ranges from "very poor" to "excellent". Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better level of functioning/quality of life.
Number of Participants Experiencing AE Burden due to Treatment as Assessed by EORTC Item Library 46 (IL46) From Day 8 up to Cycle 21 (cycle length=28 days) The EORTC IL46 is a single question that assesses bother (burden) of treatment. It is rated on a scale from 1 to 4, ranging from "not at all" to "very much".
Change from Baseline in Symptomatic Treatment Toxicities as Assessed by National Cancer Institute Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE) From Day 1 up to Cycle 21 (cycle length=28 days) The PRO-CTCAE contains 124 questions that are rated either dichotomously (for determination of presence vs. absence) or on a 5-point Likert scale (0=none to 4=very much) for determination of frequency of occurrence, severity, and interference with daily function. Treatment toxicities can occur with observable signs (e.g., vomiting) or non-observable symptoms (e.g., nausea). A subset of 16 symptoms (fatigue, chills, nausea, vomiting, diarrhea, constipation, decreased appetite, swelling, itching, rash, headache, muscle pain, joint pain, general pain, cough, and shortness of breath) will be assessed in this study.
Trial Locations
- Locations (95)
Highlands Oncology Group.
🇺🇸Springdale, Arkansas, United States
City of Hope Cancer Center
🇺🇸Duarte, California, United States
Kaiser Permanente - Riverside
🇺🇸Riverside, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Georgetown University Medical Center Lombardi Cancer Center
🇺🇸Washington, District of Columbia, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Memorial Sloan Kettering Cancer Center Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
MSK Monmouth
🇺🇸Middletown, New Jersey, United States
MSK Bergen
🇺🇸Montvale, New Jersey, United States
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